What is up your nose?

We are interested in the contents of your nose, not at the level of hair, bogey and the occasional finger, but at the level of the complex microbial community that lives there and how it is associated with respiratory infection. The makeup of this community has been interrogated through sequencing (the airway microbiome) with indications that some bacterial communities may be associated with health and others with disease.

A bacterial diet

However, what the bacteria in the airways eat to survive is less well understood. One tool that may help us to characterise which biochemicals in the airways bacteria can use as food is called metabolomics. This uses liquid chromatography, to separate the biochemicals, and then mass spectrometry, to interrogate what they are. Comparing the mass spectrometry data against a curated library, we can then determine which individual biochemicals are present and their relative abundance. This tool has been used widely to investigate changes in the blood but has not been used much to interrogate the airway.

Blotting paper 2.0

The aim of our recently published study was to compare methods for sampling the airway metabolome. We looked at two standard techniques – nasal lavage (flushing a millilitre of saline through the nose and recovering whatever you can – quite a lot never comes back!) and induced sputum (getting people to breathe in an expectorant and then spit in a cup). We also used a newer technique, that had never been used for metabolomics sampling, called Synthetic Absorptive Matrix (SAM) strips. These are hi-tech blotting paper and have been used to recover other types of sample from the airways, including antibodies and cytokines. You can watch a video of their inventor having them put up his nose here. We looked at the use of these SAM strips in both the upper airway (via the nose) and the lower airway (via a bronchoscope). In the traditions of Barry Marshall (though I doubt I will get a Nobel prize for this), I volunteered to be one of the subjects for the sampling; the nasal wash, induced sputum and upper airway SAM were all fine, but having a bronchoscopy was fairly unpleasant.

It’s good to share

Having collected the samples, we then outsourced the running of the metabolomics to a company, called Metabolon in the US. This choice had mixed reviews, but I think it is ok to outsource, increasingly labs are outsourcing some of the more specialist analysis approaches – sequencing, transcriptomics, metabolomics. This makes sense in terms of time, expertise and access to equipment. Specifically in the case of metabolomics, outsourcing gave us access to a much larger curated library of samples, giving us more information from our samples, the biochemicals were also grouped into families, enabling us to interrogate the data more easily.

Sooo much data

From the point of performing the study to publishing it has been a lengthy process. In part this was due to the complexity of the dataset. We had approximately 14,000 data points – which may be small compared to some types of project, but when you are used performing focussed studies on individual mediators it was quite a step change. This was combined with a bewildering list of biochemicals, most of which we had never heard of – 1-stearoyl-2-arachidonyl-GPC anyone? In the end, through the power of the R programming platform and a very talented PhD student, we have ended up with a paper that uses a wide range of graph types, all of which aimed to compress the data into a meaningful form.

Food for the Pseuds

So what did we find? In total, 581 biochemicals were recovered from the airways belonging to a range of different families. When we compared the relative abundance of the these biochemicals between the different sampling techniques, we saw that the SAM strips gave us a much greater recovery of biochemicals than the other approaches. Since we were interested in how the airway metabolome enables bacterial colonisation, we screened some of these biochemicals for their ability to support bacterial growth. 35 of these biochemicals were able to support growth of the opportunistic airway bacteria Pseudomonas aeruginosa, including a number of sugars and amino acids.

A microcosm in a nostril

The airways represent a fascinating ecosystem because they are nutritionally more restricted in terms of the range and specific concentrations of any one biochemical compared to say the gut, but at the same time the nutrients are constantly refreshed. The balance of biochemicals in the airways shapes the bacteria that can live there, and we believe that this could be dysregulated in disease. By developing the tools to sample the airway metabolome, we are now one step closer to understanding how changes in airway biochemistry affects infection.

How do you build resilience

This was a co-authored piece with Dr Cecilia Johansson (Imperial College London)

At the recent British Society for Immunology (BSI) Early Career Training session in London, we were tasked with talking about tools to help immunologists improve their resilience. This was identified  by the BSI’s ‘Careers in Immunology’ report as an area that early stage (and middle and late stage) immunologists struggle with throughout their careers. So you probably don’t need us to tell you that a career in science can be difficult. Whatever stage you are at, there are always new hurdles to surmount and rejections to overcome. Part of the phenotype of the successful scientist is resilience: resilience in the face of experiments failing, resilience in the face of papers being rejected, resilience in the face of short term contracts, minimal wages and a terrifying lack of job security. As resilience is "the capacity to recover quickly from difficulties" – how do we build/enhance our resilience?

We have identified three sources of resilience that you can draw upon: within yourself, outside yourself and outside your work.

The Struggle Within

The first source of resilience has to come from within yourself. There are a number of tricks that we think can help:

1. Mindset. Carol Dweck is a Professor of Psychology at Stanford University; in her book MindSet,1 she identifies the strength of a growth mindset, which means looking for the opportunities to improve yourself in any situation. So instead of saying ‘reviewer 2 is an idiot’, reframe the situation to say ‘how could I have made my writing more clear so that even reviewer 2 could understand it’.
2. Other people. Other people’s success can be a source of strength, or not: we have two different approaches to deal with it.
   1. Never compare up (John’s approach). With the internet to hand you don’t have to look very far to find a more successful immunologist than yourself. It is then very easy to slowly sink into despair as you read their endless CV of success. Don’t do this! Alice Prince at Columbia very clearly describes how people’s CVs are not an honest reflection of the route they took.2
   2. Inspiration (Cecilia’s approach). Use amazing people around you as role models. Have a lot of them and use their skills/behaviour/mindset as motivation.  
3. Behaviour. It is not what happened, it is how you react to the situation that decides the amount of resilience needed. Your values, mindset, beliefs, and current state of mind all influence how much resilience you have: when you are super stressed and over-worked it is much harder to cope. Reflect on how and why you react to a particular situation and think of how you can improve your coping strategies.
4. Celebrate. Make a point of celebrating successes big and small: papers, grants, experiments for both yourself and everyone around you. Apply the perspective of time to your progress: taking a longer view smooths out the lows and demonstrates an upward trajectory. Pause and take stock of the past three months, one year, five years and identify what went right.
5. Make plans. It is difficult to assess your progress without a plan. What do you want to achieve in the next three months, one year, five years. The granularity of the detail can fade as you look further into the future.
6. Pause and take care of yourself. In a stressful life/period, it is very easy to forget yourself. Find ways of manage your time (as time is precious and we never have enough) and your stress levels. Mindfulness (essentially meditation) can be a very helpful tool. It doesn’t need much more than closing your eyes and focusing on your breath or the background noises for a few minutes to re-wind and re-set.

All of these approaches link to good reflective practice – studying your own experiences to improve the way you work. There are times when everything can get on top of you and you have to take time to step back. However, occasionally, it is not possible to do this alone and this is where you need to the second source of resilience, other people.

Everybody needs somebody

We all need support from other people. The Ancient Greek language has multiple different words for love/ support, and while the type of support we need most will vary from person to person and with time of life, these different types provide a useful framework for thinking about our interactions with others. This support can come from both within science and from your broader circle of friends and family.

Agape refers to love from a parent to a child, but more broadly reflects support from a senior figure to someone more junior. Don’t restrict yourself to one role model or mentor, you don’t even need to have met them (e.g. CJ looks to Cheryl Sandberg, COO at Facebook3; JT has learnt a huge amount from Stephen King’s book On Writing4). Take every opportunity to meet new and inspiring people. But also look inwards, most organisations (including the BSI) run mentoring programs. And remember different people will be useful for different types of advice/perspectives.

Eros describes the love of a partner. Now this is far from being a lonely hearts column, but we both draw great strength from our partners. The family network (partner, children, parents, cousins etc) is also a huge source of support.

Finally, but not least, Phillia love of a friend. Assembling a group of like-minded individuals is really important. Start in your PhD. Long hours spent moving colourless liquid around in labs are the perfect time to bond. Immunology is not a big field: as you progress with your career, it is amazing the times your paths will cross and re-cross. If nothing else, your PhD cohort are good for free beds in foreign cities. But the hope is that you can rise together on a common mutually supportive wave.5

Hit the road Jack

The final source of support is the realisation that this is just a job. If can feel all consuming, but it is still just a job. It helps to take a broader perspective. Again this comes back to good reflective practice. In parallel it is vital to have a life outside work (more work to live than live to work). This is not always easy, especially if you are juggling work and family commitments. But find outlets that you enjoy, without feeling the pressure to excel at them: bake but don’t aim to win Bake Off, run but don’t aim to win marathons. These other activities serve the same purpose as mindfulness – they break the loop when work is getting on top of you. Try to remember why you are doing/chose to do this job and the many positive aspects it brings.

A career in immunology has peaks and troughs. It’s ok to find it tricky and to admit to other people that you find it tricky. Recognising and celebrating the highs and learning tools to negotiate the lows can really help.

John Tregoning, Senior Lecturer in Immunology, Imperial College London. Twitter: @DrTregoning

Cecilia Johansson, Senior Lecturer in Respiratory Infection, Imperial College London. Twitter: @cjohansson_lab 

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Further reading

You can read more articles from John on his blog: drtregoning.blogspot.co.uk. References for the article are below.

1. Dweck, C. S. Mindset  the new psychology of success. Updated edition. edn,  (Random House, 2016).
2. Prince, A. Omissions from a National Institute of Health (NIH) biosketch. PLoS Pathog 14, e1006896, doi:10.1371/journal.ppat.1006896 (2018).
3. Sandberg, S. Lean in: women, work, and the will to lead. First edition. edn,  (Alfred A. Knopf, 2013).
4. King, S. On writing: a memoir of the craft. Scribner trade paperback edition. edn,  (Scribner, 2010).
5. Tregoning, J. No researcher is too junior to fix science. Nature 545, 7, doi:10.1038/545007a (2017).

Buy one, get one free: Vaccinate the mother, protect the child

Flu vaccine the best way to protect

Infection with influenza virus, the causative agent of flu, is particularly severe in pregnant women and newborn children. If they do get infected, they are far more likely to get severe disease leading to hospitalisation. For the pregnant mother, the simplest approach to avoid this is to get the flu vaccine as soon as it becomes available. However, these vaccines are not licensed for children under 6 months of age – leading us to ask the question, how do we protect newborn children against influenza infection?

Maternal vaccination, protecting both mother and child

Luckily, the body has already come up with a solution. During pregnancy, mothers pass on immunity to their children. This passive protection is transferred in the form of antibodies, which are proteins made by the immune system that are highly specific for the molecules that make up the coats of viruses and can prevent the viruses from infecting our cells. This antibody transfer occurs in the second and third trimester of pregnancy and has evolved so that the newborn child has some early protection against whatever infections the mother has been exposed to. We can utilise this system with maternal vaccination. If we vaccinate the mother, she will make antibodies that recognise the virus in the vaccine and some of these antibodies will pass from her to her baby. This maternal immunisation approach has been seen to be very effective in reducing the burden of infection with tetanus and pertussis (whooping cough) in babies. Maternal immunisation has also been recommended as a method of reducing influenza infection in babies since 2005.

When is the best time to vaccinate?

One important question is when is the best point during pregnancy to vaccinate the mother to ensure the maximum transfer of antibody to the baby. It was originally thought that early in the third trimester (weeks 25-36 of pregnancy) was best as this was the peak of antibody transfer, but recent studies investigating pertussis vaccination of mothers saw higher levels in babies if the mothers were vaccinated in the second trimester (weeks 13-24 of pregnancy). We wanted to explore the best time to immunise mothers with influenza vaccine. In our latest paper, we measured the level of influenza virus specific antibodies in both mothers and babies at the time of birth. We compared babies born to mothers who were vaccinated in the first, second or third trimesters with babies born to unvaccinated mothers. We saw that there was significantly more influenza specific antibody in babies born to vaccinated mothers than in those born to unvaccinated mothers – demonstrating that maternal flu vaccination is highly effective at boosting the protection against influenza infection in the baby. We then investigated timing and observed that the high levels of antibody were seen in children born to mothers vaccinated in either the second or the third trimester, suggesting that either timepoint was equivalent, though there was less antibody transferred if the gap between vaccination and birth was less than four weeks.

Flu the ever changing

However, there is a complication with influenza virus; unlike the other pathogens for which maternal immunisation is recommended – pertussis and tetanus, the influenza virus changes. These changes in virus necessitate a new flu vaccine each year to match the viruses that are circulating. Flu is also seasonal – you are much more likely to get flu in winter months (in temperate climates). This seasonality had an effect on the levels of immune protection in our study: children born during the flu season had higher levels of antibody than those born outside it. 

The time is now

When we put the seasonality of influenza together with the best time to vaccinate mothers to pass antibody to children, we see that the current practice of offering flu vaccine to mothers as soon as it becomes available gives the best balance of protection to both mothers and their babies at the times when they need it most. This is because the flu season is 6 months long and pregnancy is nine months long. Whilst immunising mothers in the first trimester does not pass on the most antibody to the baby, immunising the mother at the start of the flu season gives the mother maximal protection for the whole flu season and they will give birth outside the flu season, so the baby requires less protection. Mothers who are in the second or third trimester at the start of the flu season will benefit from the protection of the vaccine themselves and pass antibody protection to their baby.

Therefore our study supports the current practice of offering influenza vaccine to mothers as soon as it becomes available.

No Laughing Matter: Use of humour in lectures

We were asked to come up with the best and worst examples of lecturing, either our own or those we’ve attended. Clearly my lectures are textbook examples of tertiary content delivery and probably deserve prizes (worth a try). So I thought back to when I was the recipient of lectures (a long time ago). But since I went to a research focussed university in the mid 90’s where teaching was at best seen as a chore, the quality was fairly universally m’eh. There was, however, one standout lecturer who I still remember, and not because of the content, something to do with action potentials in nerve cells (holy moly I remembered something), but because of his delivery style. Each lecture had a carefully crafted hilarious diversion (normally about walking in the Alps). This in turn got me thinking about using humour in lectures, which I try, and sometimes succeed, to do. Here are some tips:

1.       Simple is best. You don’t need to be Jonathan Swift to get a laugh out of 200 bored undergrads. To be honest, most of the jokes I use work as well with primary school audiences as they do with postgraduates (particularly my carefully curated library of pictures of snot). My most successful joke uses the power of slide animation to transform “B for boring cells” into “B for brilliant cells”, this even gets applause! But beware, jokes, if they work, disrupt the flow and it can take a couple of minutes to settle the room afterwards.

2.       Context is important. Students are not necessarily expecting humour and so may not process it as such. When, in a fit of pique, I told one cohort that their dissertations needed to be handwritten and have the first letter illustrated by monks, the course organiser had a busy afternoon reassuring them that this wasn’t the case.

3.       Be culturally aware. Most jokes work because of some common ground, knowledge or experience; which the students may not have in common with you. Age in particular is a big barrier. I started working at Imperial before most of the current students were born, so my references to pop culture often draw blank looks. I once told a PhD student that “I love it when a plan comes together” and they looked confused, apparently unaware of the wisdom of Colonel John “Hannibal” Smith.

4.       Visual jokes work, but can take time. I love cartoons and have tried to use them from a range of sources (Piled higher and deeper, sketching science and @redpenblackpen all being favourites). But cartoons take time to read - don’t just flash them up and expect instant gratification. Memes work better: since they come with a preloaded meaning, they tick the shared common ground box. They can even be educational – if Boromir is saying it, it must be true.

5.       Align with teaching. One does not simply throw in a joke and expect it to work: you need to link the joke to the content. Humour can be memorable, but it can divert memory away from what you are trying to teach. This is why 20 years later I can remember my physiology lecturer but not my physiology lectures. I managed perfect joke-content alignment once, by tenuously linking UKIP, Brexit and the EU to T cell immunology. 3 years later, the students came up and said they remembered my lecture from the first year – both the joke and the concept.

On the whole, humour is a useful tool, but there needs to be a thread, however unlikely between the learning objectives and the laughter.

This article first appeared in Times Higher Education

Turn off your e-mail and social media to get more done

Distractions are a fundamental aspect of the modern world, but we don’t have to become hermits to avoid them.

We are all busy, seemingly all the time, with a never-ending stream of e-mails to answer and meetings to attend. But are there better ways to do busy? Cal Newport, in his book Deep Work (Piatkus, 2016), says “yes”. Here’s what I’ve learnt from him.

Newport argues that, in the new world of work, the only thing we have to sell is our capacity to think rather than our capacity to do. But this ability to think does not come naturally or easily, and, unfortunately, the interconnected world that we live in throws big barriers in the way of big thinking.

Newport spends a lot of time exploring this point in Deep Work. But I suspect you need look no further than your swollen e-mail inbox or your back-to-back schedule to see that your precious time is being frittered away. And that is not counting social media, which has many ways to make us dumber: how many times have you lost a great idea, distracted by that little red Facebook notification?

The solution

Fortunately, Newport has a number of evidence-based ‘life hacks’ to combat this. Fundamentally, they come down to one thing: remove all distractions. You might think you are already doing this by turning off your phone occasionally. But you need to go further: don’t just turn off your phone; put it in a lead-lined box and bury it at the bottom of the ocean. Quit all social media. Isolate yourself from all modern life. Smash the Wi-Fi router. Move to a small island. Then, and only then, through a state of pure asceticism, might you get some work done.

However, this perfect state of deep thought might not necessarily be achievable if you want to keep your job, in which case some of the following suggestions might enable you to get the most out of your brain.

E-mail better

Shake the habit. E-mail is the worst attention thief. It has myriad means of misdirection, from the on-screen pop-up, to the envelope icon, to the alluring bold font in the unread e-mail folder. There is some ‘brain reward centre’ stuff happening with e-mail — it tells you that you are important and wanted, even if it is only an invite to write for a “presgitious new jorunal” [sic]. The easiest way to limit e-mail’s impact is to turn it off completely.

Burst transmission. That said, you still need to be in touch with the outside world. I try to limit myself to bursts. I can sustain focus for about 50 minutes, after which I reward myself with 5 minutes of e-mail, which inevitably turns into 10. No, this is not perfect and yes, resetting after 10 minutes is tricky, but it is much more effective than having the e-mail monkey on your back for the whole day.

Short and sweet. E-mail overload is universal and often exponential. ‘CC alls’, imprecise e-mails leading to immediate clarification and e-mail ‘tennis’ while trying to settle on a date all add to this burden. Making your e-mails concise and final means everyone wins. For example, instead of suggesting a time to meet, send a calendar invite directly. One question I don’t have the answer to is when to say ‘thank you’, balancing the need not to upset someone with not getting stuck in a further round of acknowledgment and counter-acknowledgement. Send better e-mail and ye shall receive better e-mail.

Do it later. E-mail is an insatiable beast; it feels like it needs immediate action: it doesn’t. Scan read, flag things for later and do it in batches.

Not now

Batching non-essential tasks can be applied to more than e-mail. I’ve found there is no way to stop the random thoughts coming, but it is possible to reduce their derailing impact. If a thought crops up, I scribble it onto a Post-it note and then batch busy work into times of the day when I am normally less productive.

Find a space

Your shared office maintained at slightly the wrong temperature, next door to a chatty neighbour with a penchant for pickled fish, might not be the ideal place to achieve the Zen of deep work. Try working elsewhere: libraries, cafes, at home. I get a surprising amount of writing done on the train to work — an added benefit of London commuters not talking to each other.

But it is not just about work. Making your brain better is more than 9 to 5. The Internet has invaded our lives to the extent that we cannot switch off. And you might argue that it is just downtime, but the habit of endlessly checking devices leads to a loop of inattention and a dilution of focus during working hours.

A lot of a scientist’s job relies on creativity, which in turn relies upon your subconscious doing some of the work. But it can’t do this when overloaded with cat videos, envious thoughts about your friends’ self-reported quality of life and pictures of someone else’s lunch. Stepping back from social and work media after certain times of day both help.

More radically, aspire to be bored. Put your phone away and if you have five spare seconds, keep them spare. Being click-baited to generate advertising income for unscrupulous publishers doesn’t do any good to you or the world.

Health warning

At the beginning of the summer, I tried the full ‘academic monk’ thing and failed. There were some mitigating circumstances for my lack of focus, but then again I’m sure there will be next summer, and the summer after that.

Clearing your head has clear benefits: better productivity; being more present with friends and family; brilliant ideas. It is also slightly addictive in itself — achieving deep focus and really working through a problem is intensely satisfying. We’re all working hard enough. It’s time to work smarter.

This is an article from the Nature Careers Community.

What are science?

Apparently we all fucking love science, or at least we love pretty pictures, anecdotal facts, chemical explosions and slightly preachy environmentalism.

However, science is none of these things. Science is the generation and testing of ideas; normally disproving them, in the process generating more ideas that need more testing.

Science junkies

Sadly, the day job of a scientist is nothing like the programs ‘Bang goes the theory/Tomorrow’s World/Johnny Ball Reveals All’ (delete as appropriate depending on your generation): in my 20 years being a professional scientist, there has been no time at work when I have blown anything up, thrown heavy weights into bowls of custard or put Mentos into bottles of Diet Coke.
To be honest, blowing things up at work is frowned upon and the management go to some lengths to prevent us blowing up the building (just another example of health and safety gone mad).
Highly visual demonstrations of chemical reactions are educational if phrased properly – if I do this, what do you think will happen and why? And these demonstrations can be effective for attracting the impressionable to a life of science. In effect, flashy chemical reactions are the gateway drug to scientific addiction.
At school we had a teacher who once a term gave us unrestricted access to the chemical store and a Bunsen burner; I imagined this was what it would be to be a scientist. Nowadays I don’t even get to do experiments, and yet I identify more as a scientist now than when I was doing my PhD as a space-filler before getting a “real job”.

Indoor work, no heavy lifting

So if the day-to-day of science isn’t setting things on fire, what is it?
It is immensely varied, and depends upon both the stage of your scientific career and the field you work in. But the main work of science is testing ideas. Some of which involves being in a lab, but most of which involves sitting in an office analysing the results from your experiments or coming up with new ideas because your experiments haven’t turned out as expected.
Since 99% of these ideas come from other people, another major strand is evaluating other people’s ideas and building on the back of them. And since other people need to evaluate the ideas we have, we need to be able to effectively communicate them, as written articles (papers), as sales pitches (grants) or in person (conferences).
So disappointingly, the day to day work of science is not so far removed from other professions, though we do get to wear a white coat occasionally. You need to be able to read, to write and, terrifyingly, interact with other people – very much none of the things that got most of us into science in the first place.

No researcher is too junior to fix science

Here is an article from Nature about how we can work together to improve science

https://www.nature.com/news/no-researcher-is-too-junior-to-fix-science-1.21928